Glaucoma, a disease characterized by intra-ocular pressure (IOP) that is too high for the preservation of a healthy optic nerve, leads to visual field loss and blindness when left untreated. Primary open angle glaucoma (POAG), the most common form of glaucoma, effects approximately 50 million people worldwide and is the leading cause of irreversible blindness. Intra-ocular pressure is currently the only modifiable risk factor for glaucoma.
Aqueous humor drains from the eye through the conventional (trabecular meshwork) and unconventional (uveoscleral) outflow systems. In patients with ocular hypertension (OHT) or glaucoma, the conventional outflow system is dysfunctional, compromising pressure regulation and leading to elevated IOP.
Topical ophthalmic IOP-lowering medications are typically the first-line therapy for glaucoma and OHT. However, patient compliance is a significant problem. Approximately half of diagnosed glaucoma patients are on more than one daily glaucoma medication and a quarter are on maximally tolerated medical therapy. Furthermore, no medications are currently clinically available that specifically target the conventional outflow system.
Laser Trabeculoplasty (LT) is commonly a second-line treatment option for POAG utilized when medications fail. LT involves the application of thermal energy to the TM to decrease IOP, but the precise mechanism of action is unknown. Although effective in approximately half of patients up to 18 months, repeat treatments show diminished effect, probably due to its destructive nature on TM cells. Data show that LT increases cytokine release from the TM and monocyte infiltration into the eye, suggesting a mechanism of action involving thermal tissue damage and a subsequent inflammatory system activation. Such thermal injury with cell death and inflammation likely underlies the diminished responsiveness of LT upon repeated treatments.
Invasive glaucoma surgery is a third-line treatment option, but it is not broadly favored due to its complication rate and lack of sustained efficacy. The most common glaucoma surgery is trabeculectomy, which involves the creation of a hole in the sclera to bypass the conventional outflow tract and drain aqueous humor into an outer bleb. However, approximately 50% of glaucoma surgery patients experience complications (e.g., infection, leakage, and irritation) and approximately 15% are likely to require a re-operation within three years.
A relatively new group of alternative treatment options called minimally invasive glaucoma surgery (MIGS) is under investigation. While less invasive than traditional glaucoma surgery, MIGS still involves an incision, may result in permanent tissue damage, and/or has mixed efficacy results. For example, trabecular micro-bypass stenting, which involves placing a micro-stent in the TM during cataract surgery, has been demonstrated to be independently less effective than cataract surgery alone.
Ultrasonic devices are being developed to apply focused ultrasound waves to the TM or ciliary body. Focused ultrasound is destructive in soft human tissue, and causes thermal and mechanical damage to ocular tissue. In both TM and ciliary body applications, target tissue is permanently damaged, such that repeat treatments are likely to be less effective, just like repeat LT treatments are less effective. In addition, safety is a concern given the potential for collateral tissue damage to critical ocular tissues (e.g., cornea). Acceptable long term safety and efficacy has yet to shown.
Thus, there is a need for, among other things, an effective, non-invasive, atraumatic and repeatable treatment option for glaucoma and OHT patients with elevated IOP that are unable to comply with their medication regimen or on maximally tolerated medication.